{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T12:22:33Z","timestamp":1783686153081,"version":"3.55.0"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T00:00:00Z","timestamp":1758067200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T00:00:00Z","timestamp":1758067200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100008769","name":"Julius-Maximilians-Universit\u00e4t W\u00fcrzburg","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008769","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Hypophosphatasia (HPP) is a rare genetic disorder mainly affecting bone and tooth mineralization in patients due to <jats:italic>ALPL<\/jats:italic> gene mutations. Understanding genotype-phenotype correlations in HPP remains challenging due to different severities and the disease\u2019s heterogeneity. To address this, we established a novel zebrafish animal model (<jats:italic>alpl<\/jats:italic>\n            <jats:sup>wue7<\/jats:sup>), which mimics severe HPP disease forms. To bypass limitations in human-based phenotypic classification of skeletal alterations in this transgenic line, we developed and trained an artificial intelligence (AI) model capable of image-based classification with 68% accuracy\u2014an improvement of 79% over manual classification. Our AI model could successfully identify early developmental alterations independent of altered image magnification, coloration quality and executing scientists. Using attention rollout, we further visualized AI decision-making, revealing not only expected focus on early bone structures but also unexpected emphasis on the otoliths\u2014parts of the zebrafish\u2019s hearing and balancing organ. We see applications of our AI system in analyzing other skeletal disorder models as well as in providing an unbiased, high-throughput phenotypic rescue quantification assay for potential drug screening applications in zebrafish larvae. Overall, our findings establish an integrated platform for studying HPP and open new avenues for AI-assisted phenotyping and therapeutic discovery.<\/jats:p>","DOI":"10.1038\/s41598-025-19199-w","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T11:57:30Z","timestamp":1758110250000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["AI-assisted phenotyping in a zebrafish hypophosphatasia model enables early and precise detection of skeletal alterations"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-9211-5870","authenticated-orcid":false,"given":"Regina","family":"Hark","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Z\u00fcrlein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3746-0123","authenticated-orcid":false,"given":"Viet T.","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6671-1380","authenticated-orcid":false,"given":"Gunther","family":"Gust","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Hekel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0934-7169","authenticated-orcid":false,"given":"Daniel","family":"Liedtke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,17]]},"reference":[{"issue":"75","key":"19199_CR1","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1001\/archpedi.1948.02030020840003","volume":"1911","author":"JC Rathbun","year":"1948","unstructured":"Rathbun, J. C. Hypophosphatasia; a new developmental anomaly. Am. J. Dis. Child 1911(75), 822\u201331 (1948).","journal-title":"Am. J. Dis. Child"},{"key":"19199_CR2","doi-asserted-by":"crossref","unstructured":"Liedtke, D., Hofmann, C., Jakob, F., Klopocki, E. & Graser, S. Tissue-nonspecific alkaline phosphatase\u2014A gatekeeper of physiological conditions in health and a modulator of biological environments in disease. Biomolecules. 10 (2020).","DOI":"10.3390\/biom10121648"},{"key":"19199_CR3","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/1750-1172-2-40","volume":"2","author":"E Mornet","year":"2007","unstructured":"Mornet, E. Hypophosphatasia. Orphanet J. Rare Diseases 2, 40. https:\/\/doi.org\/10.1186\/1750-1172-2-40 (2007).","journal-title":"Orphanet J. Rare Diseases"},{"key":"19199_CR4","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1007\/s12018-013-9139-0","volume":"11","author":"C Hofmann","year":"2013","unstructured":"Hofmann, C. et al. Clinical aspects of hypophosphatasia: An update. Clin. Rev. Bone Mineral Metabolism 11, 60\u201370. https:\/\/doi.org\/10.1007\/s12018-013-9139-0 (2013).","journal-title":"Clin. Rev. Bone Mineral Metabolism"},{"key":"19199_CR5","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1111\/j.1469-1809.2011.00642.x","volume":"75","author":"E Mornet","year":"2011","unstructured":"Mornet, E., Yvard, A., Taillandier, A., Fauvert, D. & Simon-Bouy, B. A molecular-based estimation of the prevalence of hypophosphatasia in the European population. Ann. Hum. Genet. 75, 439\u201345 (2011).","journal-title":"Ann. Hum. Genet."},{"key":"19199_CR6","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1016\/0002-9343(57)90124-9","volume":"22","author":"D Fraser","year":"1957","unstructured":"Fraser, D. Hypophosphatasia. Am. J. Med. 22, 730\u201346 (1957).","journal-title":"Am. J. Med."},{"key":"19199_CR7","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1007\/s00198-018-4691-6","volume":"30","author":"JM Colazo","year":"2019","unstructured":"Colazo, J. M., Hu, J. R., Dahir, K. M. & Simmons, J. H. Neurological symptoms in hypophosphatasia. Osteoporosis Int. 30, 469\u2013480. https:\/\/doi.org\/10.1007\/s00198-018-4691-6 (2019).","journal-title":"Osteoporosis Int."},{"key":"19199_CR8","doi-asserted-by":"publisher","first-page":"7666","DOI":"10.1073\/pnas.85.20.7666","volume":"85","author":"MJ Weiss","year":"1988","unstructured":"Weiss, M. J. et al. A missense mutation in the human liver\/bone\/kidney alkaline phosphatase gene causing a lethal form of hypophosphatasia. Proc. Natl. Acad. Sci. U.S.A. 85, 7666\u20139 (1988).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"19199_CR9","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1002\/(SICI)1098-1004(200004)15:4<309::AID-HUMU2>3.0.CO;2-C","volume":"15","author":"E Mornet","year":"2000","unstructured":"Mornet, E. Hypophosphatasia: the mutations in the tissue-nonspecific alkaline phosphatase gene. Hum. Mutat. 15, 309\u201315 (2000).","journal-title":"Hum. Mutat."},{"key":"19199_CR10","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2023.116947","volume":"178","author":"RF Mariam","year":"2024","unstructured":"Mariam, R. F. et al. The global alpl gene variant classification project: Dedicated to deciphering variants. Bone. 178, 116947 (2024).","journal-title":"Bone."},{"key":"19199_CR11","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1007\/s00774-017-0888-6","volume":"36","author":"A Taillandier","year":"2018","unstructured":"Taillandier, A. et al. Genetic analysis of adults heterozygous for alpl mutations. J. Bone Miner. Metab. 36, 723\u2013733 (2018).","journal-title":"J. Bone Miner. Metab."},{"key":"19199_CR12","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1038\/s41431-020-00732-6","volume":"29","author":"E Mornet","year":"2021","unstructured":"Mornet, E. et al. Hypophosphatasia: A genetic-based nosology and new insights in genotype\u2013phenotype correlation. Eur. J. Hum. Genet. 29, 289\u2013299 (2021).","journal-title":"Eur. J. Hum. Genet."},{"key":"19199_CR13","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1007\/s00223-015-0079-1","volume":"98","author":"JL Mill\u00e1n","year":"2016","unstructured":"Mill\u00e1n, J. L. & Whyte, M. P. Alkaline phosphatase and hypophosphatasia. Calcif. Tissue Int. 98, 398\u2013416 (2016).","journal-title":"Calcif. Tissue Int."},{"key":"19199_CR14","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1007\/s00223-012-9672-8","volume":"93","author":"JL Mill\u00e1n","year":"2013","unstructured":"Mill\u00e1n, J. L. The role of phosphatases in the initiation of skeletal mineralization. Calcif. Tissue Int. 93, 299\u2013306 (2013).","journal-title":"Calcif. Tissue Int."},{"key":"19199_CR15","doi-asserted-by":"publisher","first-page":"3147","DOI":"10.2147\/DDDT.S154922","volume":"12","author":"SA Bowden","year":"2018","unstructured":"Bowden, S. A. & Foster, B. L. Profile of asfotase alfa in the treatment of hypophosphatasia: Design, development, and place in therapy. Drug Des. Devel. Ther. 12, 3147\u20133161 (2018).","journal-title":"Drug Des. Devel. Ther."},{"key":"19199_CR16","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1007\/s00223-025-01356-y","volume":"116","author":"L Seefried","year":"2025","unstructured":"Seefried, L., Genest, F., Hofmann, C., Brandi, M. L. & Rush, E. Diagnosis and treatment of hypophosphatasia. Calcif. Tissue Int. 116, 46. https:\/\/doi.org\/10.1007\/s00223-025-01356-y (2025).","journal-title":"Calcif. Tissue Int."},{"key":"19199_CR17","doi-asserted-by":"crossref","unstructured":"Graser, S., Liedtke, D. & Jakob, F. Tnap as a new player in chronic inflammatory conditions and metabolism. Int. J. Mol. Sci. 22 (2021).","DOI":"10.3390\/ijms22020919"},{"key":"19199_CR18","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.1038\/ejhg.2014.10","volume":"22","author":"C Hofmann","year":"2014","unstructured":"Hofmann, C. et al. Unexpected high intrafamilial phenotypic variability observed in hypophosphatasia. Eur. J. Hum. Genet. 22, 1160\u20134 (2014).","journal-title":"Eur. J. Hum. Genet."},{"key":"19199_CR19","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/978-94-017-7197-9_1","volume":"76","author":"JP Salles","year":"2015","unstructured":"Salles, J. P. Clinical forms and animal models of hypophosphatasia. Subcell. Biochem. 76, 3\u201324 (2015).","journal-title":"Subcell. Biochem."},{"key":"19199_CR20","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1002\/(SICI)1097-0177(199703)208:3<432::AID-AJA13>3.0.CO;2-1","volume":"208","author":"S Narisawa","year":"1997","unstructured":"Narisawa, S., Fr\u00f6hlander, N. & Mill\u00e1n, J. L. Inactivation of two mouse alkaline phosphatase genes and establishment of a model of infantile hypophosphatasia. Develop. Dynam. 208, 432\u2013446 (1997).","journal-title":"Develop. Dynam."},{"key":"19199_CR21","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2022.116611","volume":"167","author":"H Katrin","year":"2023","unstructured":"Katrin, H. et al. Genetically engineered zebrafish as models of skeletal development and regeneration. Bone 167, 116611 (2023).","journal-title":"Bone"},{"key":"19199_CR22","doi-asserted-by":"publisher","first-page":"13321","DOI":"10.1038\/s41598-020-70152-5","volume":"10","author":"B Ohlebusch","year":"2020","unstructured":"Ohlebusch, B. et al. Investigation of alpl expression and tnap-activity in zebrafish implies conserved functions during skeletal and neuronal development. Sci. Rep. 10, 13321 (2020).","journal-title":"Sci. Rep."},{"key":"19199_CR23","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1038\/s41586-019-1064-z","volume":"568","author":"MA El-Brolosy","year":"2019","unstructured":"El-Brolosy, M. A. et al. Genetic compensation triggered by mutant mrna degradation. Nature 568, 193\u2013197 (2019).","journal-title":"Nature"},{"key":"19199_CR24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006780","volume":"13","author":"MA El-Brolosy","year":"2017","unstructured":"El-Brolosy, M. A. & Stainier, D. Y. R. Genetic compensation: A phenomenon in search of mechanisms. PLoS Genet. 13, e1006780 (2017).","journal-title":"PLoS Genet."},{"key":"19199_CR25","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1007\/978-94-017-7197-9_12","volume":"76","author":"LG Nowak","year":"2015","unstructured":"Nowak, L. G., Rosay, B., Cz\u00e9g\u00e9, D. & Fonta, C. Tetramisole and levamisole suppress neuronal activity independently from their inhibitory action on tissue non-specific alkaline phosphatase in mouse cortex. Subcell. Biochem. 76, 239\u201381 (2015).","journal-title":"Subcell. Biochem."},{"key":"19199_CR26","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1186\/s12880-022-00793-7","volume":"22","author":"HE Kim","year":"2022","unstructured":"Kim, H. E. et al. Transfer learning for medical image classification: A literature review. BMC Med. Imaging 22, 69 (2022).","journal-title":"BMC Med. Imaging"},{"key":"19199_CR27","doi-asserted-by":"publisher","DOI":"10.1016\/j.compbiomed.2020.104115","volume":"128","author":"MA Morid","year":"2021","unstructured":"Morid, M. A., Borjali, A. & Fiol, G. A scoping review of transfer learning research on medical image analysis using imagenet. Comput. Biol. Med. 128, 104115 (2021).","journal-title":"Comput. Biol. Med."},{"key":"19199_CR28","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1109\/TMI.2016.2528162","volume":"35","author":"H-C Shin","year":"2016","unstructured":"Shin, H.-C. et al. Deep convolutional neural networks for computer-aided detection: Cnn architectures, dataset characteristics and transfer learning. IEEE Trans. Med. Imaging 35, 1285\u20131298 (2016).","journal-title":"IEEE Trans. Med. Imaging"},{"key":"19199_CR29","doi-asserted-by":"publisher","first-page":"1299","DOI":"10.1109\/TMI.2016.2535302","volume":"35","author":"N Tajbakhsh","year":"2016","unstructured":"Tajbakhsh, N. et al. Convolutional neural networks for medical image analysis: Full training or fine tuning?. IEEE Trans. Med. Imaging 35, 1299\u20131312 (2016).","journal-title":"IEEE Trans. Med. Imaging"},{"key":"19199_CR30","doi-asserted-by":"publisher","first-page":"132665","DOI":"10.1109\/ACCESS.2020.3010287","volume":"8","author":"ME Chowdhury","year":"2020","unstructured":"Chowdhury, M. E. et al. Can AI help in screening viral and COVID-19 pneumonia?. IEEE Access 8, 132665\u2013132676 (2020).","journal-title":"IEEE Access"},{"key":"19199_CR31","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1038\/nature21056","volume":"542","author":"A Esteva","year":"2017","unstructured":"Esteva, A. et al. Dermatologist-level classification of skin cancer with deep neural networks. Nature 542, 115\u2013118 (2017).","journal-title":"Nature"},{"key":"19199_CR32","unstructured":"Dosovitskiy, A. et al. An image is worth 16x16 words: Transformers for image recognition at scale (2021). arXiv:https:\/\/arxiv.org\/abs\/2010.11929."},{"key":"19199_CR33","unstructured":"Bao, H., Dong, L., Piao, S. & Wei, F. Beit: Bert pre-training of image transformers (2022). arXiv:https:\/\/arxiv.org\/abs\/2106.08254."},{"key":"19199_CR34","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1007\/s11263-015-0816-y","volume":"115","author":"O Russakovsky","year":"2015","unstructured":"Russakovsky, O. et al. Imagenet large scale visual recognition challenge. Int. J. Computer Vision 115, 211\u2013252 (2015).","journal-title":"Int. J. Computer Vision"},{"key":"19199_CR35","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1080\/10520290701333558","volume":"82","author":"MB Walker","year":"2007","unstructured":"Walker, M. B. & Kimmel, C. B. A two-color acid-free cartilage and bone stain for zebrafish larvae. Biotech. Histochem. 82, 23\u20138 (2007).","journal-title":"Biotech. Histochem."},{"key":"19199_CR36","doi-asserted-by":"publisher","first-page":"1326","DOI":"10.1038\/s41592-022-01655-4","volume":"19","author":"CT Rueden","year":"2022","unstructured":"Rueden, C. T. et al. Pyimagej: A library for integrating imagej and python. Nat. Methods 19, 1326\u20131327. https:\/\/doi.org\/10.1038\/s41592-022-01655-4 (2022).","journal-title":"Nat. Methods"},{"key":"19199_CR37","unstructured":"Vaswani, A. Attention is all you need. Adv. Neural Inform. Process. Syst.(2017)."},{"key":"19199_CR38","first-page":"1877","volume":"33","author":"T Brown","year":"2020","unstructured":"Brown, T. et al. Language models are few-shot learners. Adv. Neural Inform. Process. Syst. 33, 1877\u20131901 (2020).","journal-title":"Adv. Neural Inform. Process. Syst."},{"key":"19199_CR39","unstructured":"DeepSeek-AI et al. Deepseek-v2: A strong, economical, and efficient mixture-of-experts language model (2024). arXiv:2405.04434."},{"key":"19199_CR40","doi-asserted-by":"crossref","unstructured":"Abnar, S. & Zuidema, W.\u00a0H. Quantifying attention flow in transformers. CoRR abs\/2005.00928 (2020).","DOI":"10.18653\/v1\/2020.acl-main.385"},{"key":"19199_CR41","unstructured":"Gildenblat, J. Vit-explain: Visualizing vision transformer attention. GitHub repository (2023). https:\/\/github.com\/jacobgil\/vit-explain."},{"key":"19199_CR42","doi-asserted-by":"crossref","unstructured":"He, K., Zhang, X., Ren, S. & Sun, J. Deep residual learning for image recognition. In Proceedings of the IEEE Conference on Computer Vision and Pattern Recognition (CVPR), 770\u2013778 (2016). https:\/\/ieeexplore.ieee.org\/document\/7780459.","DOI":"10.1109\/CVPR.2016.90"},{"key":"19199_CR43","unstructured":"learn developers, S. Roc auc score (2024). https:\/\/scikit-learn.org\/stable\/modules\/generated\/sklearn.metrics.roc_auc_score.html. Accessed on February 19, 2025"},{"key":"19199_CR44","doi-asserted-by":"publisher","first-page":"1172933","DOI":"10.3389\/fcell.2023.1172933","volume":"11","author":"S Baeza-Loya","year":"2023","unstructured":"Baeza-Loya, S. & Raible, D. W. Vestibular physiology and function in zebrafish. Front. Cell Dev. Biol. 11, 1172933 (2023).","journal-title":"Front. Cell Dev. Biol."},{"key":"19199_CR45","doi-asserted-by":"crossref","unstructured":"Patrick, P., H\u00e9l\u00e8ne, Gilles, B. & Nicole, M.-G. Endolymph chemistry and otolith growth in fish. Comptes. Rendus. Palevol. 3, 535\u2013547 (2004).","DOI":"10.1016\/j.crpv.2004.07.013"},{"key":"19199_CR46","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1126\/science.1088443","volume":"302","author":"C S\u00f6llner","year":"2003","unstructured":"S\u00f6llner, C. et al. Control of crystal size and lattice formation by starmaker in otolith biomineralization. Science 302, 282\u20136 (2003).","journal-title":"Science"},{"key":"19199_CR47","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.mod.2019.04.001","volume":"157","author":"KD Thiessen","year":"2019","unstructured":"Thiessen, K. D. et al. Zebrafish otolith biomineralization requires polyketide synthase. Mech. Dev. 157, 1\u20139 (2019).","journal-title":"Mech. Dev."},{"key":"19199_CR48","doi-asserted-by":"publisher","first-page":"1815","DOI":"10.1007\/s00198-021-05885-8","volume":"32","author":"R Garcia-Carretero","year":"2021","unstructured":"Garcia-Carretero, R. et al. Predictive modeling of hypophosphatasia based on a case series of adult patients with persistent hypophosphatasemia. Osteoporos. Int. 32, 1815\u20131824 (2021).","journal-title":"Osteoporos. Int."},{"key":"19199_CR49","doi-asserted-by":"crossref","unstructured":"Bergen, D. J.\u00a0M., Kague, E. & Hammond, C.\u00a0L. Zebrafish as an emerging model for osteoporosis: A primary testing platform for screening new osteo-active compounds. Front. Endocrinol. (Lausanne). 10, 6 (2019).","DOI":"10.3389\/fendo.2019.00006"},{"key":"19199_CR50","doi-asserted-by":"crossref","unstructured":"Tonelli, F. et al. Zebrafish: A resourceful vertebrate model to investigate skeletal disorders. Front. Endocrinol. 11 (2020).","DOI":"10.3389\/fendo.2020.00489"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-19199-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-19199-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-19199-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T00:03:24Z","timestamp":1758499404000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-19199-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,17]]},"references-count":50,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["19199"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-19199-w","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,17]]},"assertion":[{"value":"23 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 September 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All procedures involving experimental animals were performed in compliance with local animal welfare laws (Tierschutzgesetz \u00a711, Abs. 1, Nr. 1 and corresponding TierSchVersV, husbandry permit number 568\/300-1870\/13), European Union animal welfare guidelines (EU directive 2010\/63\/EU), and best-practice scientific policies (ARRIVE guidelines). Establishment and propagation of alpl transgenic lines has been approved by the Regierung von Unterfranken (permit number 55.2.2-2532-2-1472). In addition, methods of adult genotyping by Fin-clip (55.2.2-2532-2-1637) and propagation of potential harmful transgenic lines (55.2.2-2532-2-1682) have been separately approved. No preselection on sex or other biological characteristics have been performed during the presented experiments. Experiments including early embryonic stages of development have been performed in zebrafish larvae younger than 120 hpf and have been terminated timely before free-swimming and independent feeding larval stages. Procedures involving transgenic animals were in addition performed according to local regulations on this topic (Gentechnikrecht\/Gentechnik-Sicherheitsverordnung).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval and consent to participate"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"32578"}}